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C1-TEN is a negative regulator of the Akt/PKB signal transduction pathway and inhibits cell survival, proliferation, and migration

Hafizi, Sassan LU ; Ibraimi, Filiz LU and Dahlbäck, Björn LU (2005) In FASEB Journal 19(8). p.971-971
Abstract
We have previously identified C1 domain-containing phosphatase and TENsin homologue (C1-TEN) as being an intracellular binding partner for Axl receptor tyrosine kinase (RTK). C1-TEN is a tensin-related protein that houses an N-terminal region with predicted structural similarity to PTEN. Here, we report our observations on the effects of ectopic expression of C1-TEN in HEK293 cells, which resulted in profound molecular and phenotypic changes. Stable expression of C1-TEN altered cellular morphology, with less cell spreading and weaker filamentous actin staining. Cells overexpressing C1-TEN were inhibited greatly in their proliferation and migration rates as compared with mock-transfected cells. Furthermore, serum starvation-induced... (More)
We have previously identified C1 domain-containing phosphatase and TENsin homologue (C1-TEN) as being an intracellular binding partner for Axl receptor tyrosine kinase (RTK). C1-TEN is a tensin-related protein that houses an N-terminal region with predicted structural similarity to PTEN. Here, we report our observations on the effects of ectopic expression of C1-TEN in HEK293 cells, which resulted in profound molecular and phenotypic changes. Stable expression of C1-TEN altered cellular morphology, with less cell spreading and weaker filamentous actin staining. Cells overexpressing C1-TEN were inhibited greatly in their proliferation and migration rates as compared with mock-transfected cells. Furthermore, serum starvation-induced apoptosis caused a twofold increase in caspase 3 activity in C1-TEN-overexpressing cells vs. mock cells. In addition, C1-TEN-overexpressing cells showed a markedly reduced phosphorylation of Akt/PKB kinase and its substrate GSK3, as well as reduced Akt enzymatic activity. No such effects on JNK were observed. Also, serum-stimulated activation of Akt was delayed in C1-TEN-overexpressing cells, while no difference in profile of ERK activation was observed. Furthermore, cells expressing a C1-TEN mutant where the putative phosphatase active site cysteine at position 231 was substituted for a serine displayed full restoration of both cell proliferation and Akt activation. In conclusion, C1-TEN appears to be a novel intracellular phosphatase that negatively regulates the Akt/PKB signaling cascade, and is similar to its relative PTEN in this respect. However, the particular domain organization of C1-TEN may enable it to regulate RTK and other signaling complexes that are linked to Akt/PKB signaling in a unique manner. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
receptor tyrosine kinase, Ax1, phosphatase, tensin
in
FASEB Journal
volume
19
issue
8
pages
971 - 971
publisher
The Federation of American Societies for Experimental Biology
external identifiers
  • wos:000228865300022
  • scopus:20444433205
ISSN
1530-6860
DOI
10.1096/fj.04-2532fje
language
English
LU publication?
yes
id
6a56b040-d7c9-4c60-b7eb-3a16cc2fded7 (old id 243748)
date added to LUP
2007-08-07 13:51:33
date last changed
2017-10-08 04:13:31
@article{6a56b040-d7c9-4c60-b7eb-3a16cc2fded7,
  abstract     = {We have previously identified C1 domain-containing phosphatase and TENsin homologue (C1-TEN) as being an intracellular binding partner for Axl receptor tyrosine kinase (RTK). C1-TEN is a tensin-related protein that houses an N-terminal region with predicted structural similarity to PTEN. Here, we report our observations on the effects of ectopic expression of C1-TEN in HEK293 cells, which resulted in profound molecular and phenotypic changes. Stable expression of C1-TEN altered cellular morphology, with less cell spreading and weaker filamentous actin staining. Cells overexpressing C1-TEN were inhibited greatly in their proliferation and migration rates as compared with mock-transfected cells. Furthermore, serum starvation-induced apoptosis caused a twofold increase in caspase 3 activity in C1-TEN-overexpressing cells vs. mock cells. In addition, C1-TEN-overexpressing cells showed a markedly reduced phosphorylation of Akt/PKB kinase and its substrate GSK3, as well as reduced Akt enzymatic activity. No such effects on JNK were observed. Also, serum-stimulated activation of Akt was delayed in C1-TEN-overexpressing cells, while no difference in profile of ERK activation was observed. Furthermore, cells expressing a C1-TEN mutant where the putative phosphatase active site cysteine at position 231 was substituted for a serine displayed full restoration of both cell proliferation and Akt activation. In conclusion, C1-TEN appears to be a novel intracellular phosphatase that negatively regulates the Akt/PKB signaling cascade, and is similar to its relative PTEN in this respect. However, the particular domain organization of C1-TEN may enable it to regulate RTK and other signaling complexes that are linked to Akt/PKB signaling in a unique manner.},
  author       = {Hafizi, Sassan and Ibraimi, Filiz and Dahlbäck, Björn},
  issn         = {1530-6860},
  keyword      = {receptor tyrosine kinase,Ax1,phosphatase,tensin},
  language     = {eng},
  number       = {8},
  pages        = {971--971},
  publisher    = {The Federation of American Societies for Experimental Biology},
  series       = {FASEB Journal},
  title        = {C1-TEN is a negative regulator of the Akt/PKB signal transduction pathway and inhibits cell survival, proliferation, and migration},
  url          = {http://dx.doi.org/10.1096/fj.04-2532fje},
  volume       = {19},
  year         = {2005},
}